Microtubule buckling in an elastic matrix with quenched disorder

The intracellular elastic matrix has been recognized as an important factor to stabilize microtubules and increase their critical buckling force in vivo. This phenomenon was qualitatively explained by the Winkler model, which investigated buckling of a filament embedded in a homogeneous elastic medium. However, the assumption of homogeneity of the matrix in Winkler's, and other advanced models, is unrealistic inside cells, where the local environment is highly variable along the filament. Considering this to be a quenched-disorder system, we use a Poisson distribution for confinements, and apply the replica technique combined with the Gaussian variational method to address the buckling of a long filament. The results show two types of filament buckling: one corresponding to the first-order, and the other to a continuous second-order phase transition. The critical point, i.e. the switch from first- to second-order buckling transition, is induced by the increase in disorder strength. We also discover that this random disorder of the elastic environment destabilizes the filament by decreasing $P_c$ from the Winkler result, and the matrix with stronger mean elasticity has a stronger role of disorder (inhomogeneity). For microtubules in vivo, buckling follows the discontinuous first-order transition, with the threshold reduced to the fraction between 0.9 and 0.75 of the Winkler prediction for the homogeneous elastic matrix. We also show that disorder can affect the force-displacement relationship at non-zero temperature, while at zero temperature this effect vanishes.This work has been supported by the Theory of Condensed Matter Critical Mass Grant from EPSRC (EP/J017639)

Stiffening of under-constrained spring networks under isotropic strain

Disordered spring networks are a useful paradigm to examine macroscopic mechanical properties of amorphous materials. Here, we study the elastic behavior of under-constrained spring networks, i.e.\ networks with more degrees of freedom than springs. While such networks are usually floppy, they can be rigidified by applying external strain. Recently, an analytical formalism has been developed to predict the mechanical network properties close to this rigidity transition. Here we numerically show that these predictions apply to many different classes of spring networks, including phantom triangular, Delaunay, Voronoi, and honeycomb networks. The analytical predictions further imply that the shear modulus $G$ scales linearly with isotropic stress $T$ close to the rigidity transition; however, this seems to be at odds with recent numerical studies suggesting an exponent between $G$ and $T$ that is smaller than one for some network classes. Using increased numerical precision and shear stabilization, we demonstrate here that close to the transition linear scaling, $G\sim T$, holds independent of the network class. Finally, we show that our results are not or only weakly affected by finite-size effects, depending on the network class.Comment: 17 pages, 10 figure

Hard-wall entropic effect accelerates detachment of adsorbed polymer chains.

Many previous studies of unbinding kinetics have focused on a two-state model, with fully bonded and free states, which may not extend to more complicated biopolymer dynamics involving other reactions. Here we address the kinetic rate of this process at the segment level, as it is influenced by a growing dangling end of the chain. We use the mean first-passage time approach and treat the polymer as a chain attached to a wall through a succession of spring potentials, with two distinct regions of bonded and free segments. The interaction between the wall and free-moving chain end adds an entropic repulsion to this process. We estimate the average monomer detachment rate K as a function of the free dangling length L. For a flexible polymer, we find an acceleration factor in the average detachment rate depending on L and the details of the spring bond; when L is long, this factor is a simple ratio of its breaking distance to the natural bond length. For a semiflexible filament, we examine the regime where L is shorter than persistence length L_{p}, as the limit opposite to that of the flexible chain. An enhancing factor also appears, speeding up the filament unbinding when the free length grows; for a long rigid rod, this factor becomes two, independently of the bond details. We also examine the total unbinding time of an irreversible detaching process by integrating (1/K) over polymer length and discover that its power-law scaling with chain length is smaller than one, over the commonly seen range of polymer size.This work is funded by the Theory of Condensed Matter Critical Mass Grant from EPSRC (EP/J017639)

Structural effects of cap, crack, and intrinsic curvature on the microtubule catastrophe kinetics.

Microtubules (MTs) experience an effect called "catastrophe," which is the transition from the MT growth to a sudden dramatic shrinkage in length. The straight guanosine triphosphate (GTP)-tubulin cap at the filament tip and the intrinsic curvature of guanosine diphosphate (GDP)-tubulins are known to be the key thermodynamic factors that determine MT catastrophe, while the hydrolysis of this GTP-cap acts as the kinetic control of the process. Although several theoretical models have been developed, assuming the catastrophe occurs when the GTP-cap shrinks to a minimal stabilizing size, the structural effect of the GTP-cap and GDP-curvature is not explicitly included; thus, their influence on catastrophe kinetics remains less understood. To investigate this structural effect, we apply a single-protofilament model with one GTP-cap while assuming a random hydrolysis mechanism and take the occurrence of a crack in the lateral bonds between neighboring protofilaments as the onset of the catastrophe. Therein, we find the effective potential of the tip along the peel-off direction and formulate the catastrophe kinetics as a mean first-passage time problem, subject to thermal fluctuations. We consider cases with and without a compressive force on the MT tip, both of which give a quadratic effective potential, making MT catastrophe an Ornstein-Uhlenbeck process in our formalism. In the free-standing case, the mean catastrophe time has a sensitive tubulin-concentration dependence, similar to a double-exponential function, and agrees well with the experiment. For a compressed MT, we find a modified exponential function of force that shortens the catastrophe time.EPSRC EP/J01763

Bis(μ-trimethyl­silanolato-κ2 O:O)bis­{[2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentyl­phenolato-κ2 N,O]zinc}

The binuclear title complex, [Zn2(C22H28N3O)2(C3H9OSi)2], has a crystallographic imposed centre of symmetry. The ZnII atom is coordinated by three O and one N atom from one 2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentyl­phenolate ligand and two bridging trimethyl­silanolate anions in a distorted tetra­hedral geometry. The dihedral angle between the benzotriazole ring system and the benzene ring is 19.83 (5)°. The tert-pentyl groups are disordered over two orientations with refined site-occupancy ratios of 0.858 (4):0.142 (4) and 0.665 (6):0.335 (6)

Cellular apoptosis susceptibility (CSE1L/CAS) protein in cancer metastasis and chemotherapeutic drug-induced apoptosis

The cellular apoptosis susceptibility (CSE1L/CAS) protein is highly expressed in cancer, and its expression is positively correlated with high cancer stage, high cancer grade, and worse outcomes of patients. CSE1L (or CAS) regulates chemotherapeutic drug-induced cancer cell apoptosis and may play important roles in mediating the cytotoxicities of chemotherapeutic drugs against cancer cells in cancer chemotherapy. CSE1L was originally regarded as a proliferation-associated protein and was thought to regulate the proliferation of cancer cells in cancer progression. However, the results of experimental studies showed that enhanced CSE1L expression is unable to increase proliferation of cancer cells and CSE1L regulates invasion and metastasis but not proliferation of cancer cells. Recent studies revealed that CSE1L is a secretory protein, and there is a higher prevalence of secretory CSE1L in the sera of patients with metastatic cancer. Therefore, CSE1L may be a useful serological marker for screening, diagnosis and prognosis, assessment of therapeutic responses, and monitoring for recurrence of cancer. In this paper, we review the expression of CSE1L in cancer and discuss why CSE1L regulates the invasion and metastasis rather than the proliferation of cancer

Sustainable Solution for Shoring Method of Cross-Creek Bridge in Ankeng MRT System in New Taipei City: A Case Study

In the Ankeng Light Rail MRT system (ALRMS) project, the U7 box girder passes crossing the Erbads creek and needs a temporary supporting system for the construction work.  In this study, three temporary shoring system options were proposed to be the construction method.  The D-B Contractor, New Asia construction and Development Corporation, evaluated and selected the optimal choice, The Steel truss frame with supporting beams, to serve as the temporary supporting system.  Compare the deflection of Δmax and Δactual, which are 1.609 cm and 1.59 cm, respectively.  This result presented that the shoring system composed of the H912*302*18*37 supporting beams and steel truss frame had achieved outstanding performance and work to construct the U7 box girder.  This paper presents how the three options are evaluated and the detailed construction processes along with the survey verification for the method

Seizure After Local Anesthesia for Nasopharyngeal Angiofibroma

We report a young male patient who experienced seizure after local injection of 3 mL 2% lidocaine with epinephrine 1:200,000 around a recurrent nasal angiofibroma. After receiving 100% oxygen via mask and thiamylal sodium, the patient had no residual neurologic sequelae. Seizure immediately following the injection of local anesthetics in the nasal cavity is probably due to injection into venous or arterial circulation with retrograde flow to the brain circulation. Further imaging study or angiography should be done before head and neck surgeries, especially in such highly vascular neoplasm

Nonlocal Particles as Strings

We find nonlocal particle theories with two dimensional conformal symmetry, including examples equivalent to the bosonic open string and closed string. This work provides a new approach to construct solvable consistent backgrounds in string theory.Comment: 25 pages, Latex, minor change